The problems inherent in precisely determining the anatomic location and extent of the thrombus in thrombovascular disease are well known. Many techniques have been developed for the purpose. Imaging the thrombus with radiolabeled fibrinogen and various other radiopharmaceuticals have been found insufficiently sensitive and/or specific. The use of platelets directly labeled with radioactive nuclides has been attempted; however, this technique has also not gained widespread use because of the complexity of the labeling procedure. Furthermore the low target to background ratios often require either delayed imaging or background subtraction to obtain suitable results.
Radiolabeling techniques for proteins are well known. Many radiolabels may be used either directly as in the case of, say, sodium .sup.125 I, .sup.125 I or .sup.131 I, or indirectly wherein the protein is first conjugated with, say, diethylene triamine pentaacetic acid (DTPA) cyclic anhydride, to which indium-111 is then chelated. It would be desirable therefore to provide a simple technique whereby a protein could be radiolabeled with a short-lived nuclide suitable for imaging and this intermediate then coupled to the platelets in such a way that they would bind to the thrombi in sufficient quantity to be located by well known scanning techniques.
Coller et al., (J. Clin. Invest., 72, 325 (1983)) developed a monoclonal antibody (10E5) that completely blocked the binding of fibrinogen to platelets. The three clones having the most potent antibodies as reported on page 327, column 1 of the Coller paper, were not found to react with dog blood platelets. This is not an irrelevant matter, since it is not generally permissible to carry out human testing of a novel pharmaceutical without previous animal testing thereof. Thus, it may not be possible to determine the ultimate human utility of the 10E5 antibody disclosed by Coller in his paper because of said regulatory prohibitions. Thus, it would be desirable to provide monoclonal antibodies that not only have the properties of the 10E5 monoclonal antibody but also react with test animal platelets so that in vivo testing thereof prior to human testing, could be carried out.